Autoimmune diseases are disorders of abnormally accelerating immune responses to self tissues and are generally treated with steroid administration and further treated with continuous administration of immunosuppressive agents such as cyclosporin and methotrexate. These agents, however, not only suppress the autoimmune response, but also suppress immune responses to pathogen infections. Consequently, the management of administration of such agents imposes a burden on patients and medical personnel.
PD-1 is an immunosuppressive receptor belonging to an immunoglobulin family and is a molecule having a function of suppressing the immune activation signals of T-cells activated by stimulation through an antigen receptor. For example, analysis of PD-1 knock-out mice demonstrates that PD-1 signals play important roles in suppression of autoimmune diseases such as autoimmune dilated cardiomyopathy, lupus-like syndrome, autoimmune encephalomyelitis, systemic lupus erythematosus, graft-versus-host disease, type I diabetes mellitus, and rheumatoid arthritis. Accordingly, an agent enhancing the PD-1 signal, that is, a PD-1 agonist is a prophylactic or therapeutic agent for autoimmune diseases.
PD-1 bispecific antibodies (Patent Literatures 1 to 3) have been recognized as a PD-1 agonist. The bispecific antibodies are composed of an antigen-recognition site of an antibody recognizing CD3 and an antigen-recognition site of an antibody recognizing PD-1 linked to each other using genetic engineering. The CD3 is a member of a T-cell receptor complex. The bispecific antibodies enhance the inhibitory signal of PD-1 against the T-cell receptor complex by increasing the frequency of bringing the PD-1 to the periphery of the T-cell receptor complex. Patent Literatures 1 to 3 also state that PD-1 bispecific antibodies can be used for prophylaxis or therapy of autoimmune diseases.
However, there is no knowledge about prescription of PD-1 agonist, to sustain the therapeutic effects with a small number of times of administration and thereby to reduce the burden of administration to patients while lowering the risk of infections.